Abstract:

Purinergic signalling, adenosine 5’-triphosphate (ATP) as an extracellular signalling molecule, was proposed in 1972. However, it was not generally accepted until the early 1990s when receptors for ATP and its breakdown product adenosine were cloned and characterised. Four P1 (adenosine) receptors are recognised (A1, A2A, A2B and A3), seven P2X ion channel receptors (P2X1-7) and eight P2Y G protein-coupled receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14). The purinergic signalling field is now widely accepted and expanding in many different directions. The weak regenerative capacity of injured neurons is an obstacle for neural repair, although the neonatal brain has a greater capacity for recovery than the adult brain. Purinergic drugs have been used to promote regeneration of injured and degenerating nerves in the brain and spinal cord. A signalling molecule, protein kinase B/Akt, regulates cell survival, growth and metabolism and inhibits apoptosis, and traumatic brain injury activates Akt. When cortical astrocytes were subjected to trauma or mechanical strain, ATP was released and there was Akt activation. PPADS, a P2 receptor antagonist, attenuated the Akt activation. Trauma-induced activation of purinergic signaling in astrocytes via P2Y4 receptors stimulates the synthesis and release of thrombospondin-1, an extracellular matrix molecule that induces synapse formation during development. This may play a role in CNS repair and remodelling after injury.